Bcl-2 breathes life into embryogenesis.
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Animals↗
Biomedical subjects
R Baer
Publications and source records attributed to R Baer.
Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA-binding activity.
The TAL2 gene is activated as a result of the (7;9) (q34;q32) translocation, a chromosome defect found in the malignant cells of some patients with T-cell acute lymphoblastic leukemia (T-ALL). TAL2 potentially encodes a basic helix-loop-helix motif that is highly related to those specified by TAL1 and LYL1, distinct genes that have also been implicated in T-ALL. In this report we show that leukemic cells bearing the (7;9) (q34;q32) translocation express a TAL2 gene product of 108 amino acids. In leukemic cells this product exists in both a phosphorylated (pp13TAL2) and an unphosphorylated (p12TAL2) form. Serine residue 100 is the major site of TAL2 phosphorylation in vivo, and it serves as an effective in vitro substrate for mitogen-activated protein (MAP) kinases such as ERK1. TAL2 polypeptides interact in vivo with the E2A gene products (E47 and E12) to form bHLH heterodimers that bind DNA in a sequence-specific manner. The TAL2 polypeptides do not bind DNA by themselves, however, suggesting that their functional properties may be contingent upon association with other bHLH proteins. Taken together, the properties of TAL2 evaluated here broadly resemble those described previously for TAL1, and therefore support the idea that both proteins promote T-ALL by a common mechanism.
Base Sequence↗
Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study.
Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.
Adolescent↗
Phosphorylation of the TAL1 oncoprotein by the extracellular-signal-regulated protein kinase ERK1.
Alteration of the TAL1 gene is the most common genetic lesion found in T-cell acute lymphoblastic leukemia. TAL1 encodes phosphoproteins, pp42TAL1 and pp22TAL1, that represent phosphorylated versions of the full-length (residues 1 to 331) and truncated (residues 176 to 331) TAL1 gene products, respectively. Both proteins contain the basic helix-loop-helix motif, a DNA-binding and protein dimerization motif common to several known transcriptional regulatory factors. We now report that serine residue 122 (S122) is a major phosphorylation site of pp42TAL1 in leukemic cell lines and transfected COS1 cells. In vivo phosphorylation of S122 is induced by epidermal growth factor with a rapid time course that parallels activation of the ERK/MAP2 protein kinases. Moreover, S122 is readily phosphorylated in vitro by the extracellular signal-regulated protein kinase ERK1. These data suggest that TAL1 residue S122 serves as an in vivo substrate for ERK/MAP2 kinases such as ERK1. Therefore, S122 phosphorylation may provide a mechanism whereby the properties of TAL1 polypeptides can be modulated by extracellular stimuli.
Amino Acid Sequence↗
TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia.
TAL1 gene rearrangement is the most common genetic defect associated with T cell acute lymphoblastic leukaemia (T-ALL). Tumour-specific rearrangements of TAL1 arise as a result of either chromosome translocation or local DNA recombination. TAL1 gene products possess the basic helix-loop-helix (bHLH) motif, a DNA-binding domain common to several known transcription factors. The bHLH domain of TAL1 is especially homologous to those encoded by TAL2 and LYL1, distinct genes that were also identified on the basis of chromosomal rearrangement in T-ALL. Thus, TAL1, TAL2 and LYL1 constitute a unique family of bHLH proteins, each of which is a potential mediator of T cell leukaemogenesis.
Amino Acid Sequence↗
Expression of the TAL1 proto-oncogene in cultured endothelial cells and blood vessels of the spleen.
The TAL1 proto-oncogene encodes a basic helix-loop-helix (bHLH) protein that has been implicated in the pathogenesis of T-cell acute lymphoblastic leukemia. Normal expression of TAL1 is observed in erythrocytic, megakaryocytic and mastocytic cells of the hematopoietic lineage. We now report that both RNA transcripts and polypeptide products of TAL1 are present in human umbilical vein endothelial cells cultured in vitro. Moreover, in situ hybridization revealed a restricted pattern of TAL1 expression in endothelial cells in vivo, including vessels within the white pulp and follicles of the spleen. In view of its presumptive role as a transcriptional factor, the TAL1 gene product may serve during normal development as a regulator of endothelial cell growth or differentiation.
Basic Helix-Loop-Helix Proteins↗
Products of the TAL1 oncogene: basic helix-loop-helix proteins phosphorylated at serine residues.
TAL1 gene rearrangement is observed in nearly 30% of patients with T-cell acute lymphoblastic leukemia (T-ALL), and thus it represents the most common genetic lesion associated with this disease. Nevertheless, the presence of TAL1 gene products in normal or leukemic cells has not been reported. Therefore, immunoprecipitation with anti-TAL1 antisera was used to demonstrate the presence of TAL1 phosphoproteins, pp42TAL1 and pp22TAL1, in both T-ALL and erythroleukemia cell lines. The pp42TAL1 and pp22TAL1 proteins appear to be phosphorylated forms of full-length and truncated TAL1 gene products respectively. Phosphoamino acid analysis revealed that pp42TAL1 contains phosphoserine residues. The TAL1 phosphoproteins were detected in all of the T-ALL cell lines that harbor obvious TAL1 gene rearrangements. Interestingly, pp42TAL1 and pp22TAL1 were also present in some, but not all, of the T-ALL lines without detectable TAL1 gene alterations. Therefore, TAL1 activation may promote leukemogenesis in a far greater proportion of T-ALL patients than the 30% that bear gross TAL1 gene rearrangements.
Basic Helix-Loop-Helix Proteins↗
HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma.
An important family of regulatory molecules is made up of proteins that possess the DNA-binding and dimerization motif known as the basic helix-loop-helix (bHLH) domain. The bHLH family includes subgroups of closely related proteins that share common functional properties and overlapping patterns of expression (e.g., the MyoD1 and achaete-scute subgroups). In this report we describe HEN1 and HEN2, mammalian genes that encode a distinct subgroup of bHLH proteins. The HEN1 gene was identified on the basis of cross-hybridization with TAL1, a known bHLH gene implicated in T-cell acute lymphoblastic leukemia. In situ fluorescence hybridization was used to localize the human HEN1 gene to chromosome band 1q22. HEN1 and HEN2 are coexpressed in the IMR-32 human neuroblastoma cell line, and they encode highly related proteins of 133 and 135 residues, respectively, that share 98% amino acid identity in their hHLH domains. These data imply that the bHLH protein subgroup encoded by HEN1 and HEN2 may serve important regulatory functions in the developing nervous system.
Amino Acid Sequence↗
The translocation (1;14)(p34;q11) in human T-cell leukemia: chromosome breakage 25 kilobase pairs downstream of the TAL1 protooncogene.
Nearly 30 percent of patients with T-cell acute lymphoblastic leukemia (T-ALL) exhibit a tumor-specific rearrangement of the TAL1 gene (also called TCL5 or SCL). These rearrangements are generated by either local DNA deletion or a (1;14)(p34;q11) chromosome translocation, and they typically result in structural alterations of the TAL1 transcription unit. In this report we present a molecular characterization of the t(1;14)(p34;q11) from a T-ALL patient. As a consequence of the translocation, TAL1 is transposed from its normal position on chromosome 1 into the T-cell receptor alpha/delta chain locus on chromosome 14. Unlike previous cases, the chromosome 1 breakpoint in this patient did not disrupt the continuity of the TAL1 transcription unit, but instead occurred approximately 25 kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant alteration of TAL1 can be mediated by long-range cis-activating mechanisms that are triggered by DNA rearrangement at a distant site. Genes Chrom Cancer 4:211-216 (1992).
Base Sequence↗
Regulating behavioral procedures for individuals with handicaps: review of state department standards.
We reviewed standards (i.e., mandatory policies or recommended guidelines) from 39 state departments of special education and 41 state departments of developmental disabilities/mental retardation (DD/MR) to determine how they addressed the use of behavioral procedures. Results indicated that many standards described procedures to change behaviors of individuals with handicaps and identified ways to regulate usage. Major findings were that (a) standards from state departments of DD/MR addressed behavioral procedures more frequently than standards from special education departments; (b) many standards addressed procedures to decrease, but not increase, behavior; (c) several standards identified safeguards to clients' rights, such as prior approval requirements and periodic review of behavioral procedures' effects; (d) some standards prohibited and/or restricted the use of specific procedures, such as those judged to be aversive; (e) about one-fifth of special education standards and two-thirds of DD/MR standards described staff training requirements for using some procedures; and (f) relatively few standards used decision models to select behavioral procedures. Implications of these findings for policy makers, service providers, and future research efforts are discussed.
Aversive Therapy↗
Enhancer-binding activity of the tal-1 oncoprotein in association with the E47/E12 helix-loop-helix proteins.
Almost 30% of patients with T-cell acute lymphoblastic leukemia (T-ALL) bear structural alterations of tal-1, a presumptive proto-oncogene that encodes sequences homologous to the helix-loop-helix (HLH) DNA-binding and dimerization domain. Analysis of the tal-1 gene product reveals that its HLH domain mediates protein-protein interactions with either of the ubiquitously expressed HLH proteins E47 and E12. The resultant tal-1/E47 and tal-1/E12 heterodimers specifically recognize the E-box DNA sequence motif found in eucaryotic transcriptional enhancers. Hence, the tal-1 protein shares biochemical properties with other tissue-specific HLH proteins that control cell type determination during myogenesis (e.g., MyoD1) and neurogenesis (e.g., achaete-scute). The data suggest that HLH heterodimers involving tal-1 may function in vivo as transcriptional regulatory factors that influence cell type determination during hematopoietic development.
Base Sequence↗
Reference price: a tool for pricing new healthcare services.
The convergent validity and scale reliability of three measures of Reference Price (R-Price) were assessed for a "new" healthcare service using an adult sample. The Pearson correlation, Cronbach's alpha and Factor analysis results indicate that the multiple scale R-Price measure exhibits both reliability and convergent validity. As a result, the R-price scale could be used as an additional input for estimating demand of a healthcare service at a given price. The paper also draws some managerial implications for healthcare professionals.
Adult↗
Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia.
The tal-1 proto-oncogene encodes a helix-loop-helix DNA-binding protein that has been implicated in the formation of T cell acute lymphoblastic leukemia (T-ALL). Patients with T-ALL harbor structural rearrangements of tal-1 that result from either local DNA deletion or t(1;14)(p34;q11) chromosome translocation. By analyzing t(1;14)(p34;q11) chromosomes from a series of patients, we have now identified a discrete region of tal-1 wherein most of the translocation breakpoints occur. Moreover, mapping of tal-1 genomic DNA revealed that coding exons are situated on both sides of the t(1;14)(p34;q11) major breakpoint region. Hence, the translocated allele of tal-1 is truncated in a manner that reduces its amino acid coding potential.
Adult↗
[Nursing care, legal incapacitation, guardianship. Basic principles of legal reform].
If in the case of a person suffering from a mental disturbance or a major physical handicap, a long-term diminishment or loss of his ability to take reasonable care of his own legal affairs should occur, legal steps can be taken which since the beginning of the century have remained largely unchanged. A new law now takes account of the altered situation. In place of "incapacitation" (Entmündigung) and "guardianship" (Pflegschaft), the term "care" (Betreuung) has now been introduced, which has an effect on the question of the person's ability to conduct his own affairs only in exceptional cases. Basic aspects of this new law are considered from a psychiatric point of view.
Aged↗
The chromosome translocation (11;14)(p13;q11) associated with T cell acute leukemia. Asymmetric diversification of the translocational junctions.
The t(11;14)(p13;q13) translocation associated with T cell acute lymphocytic leukemia generates two abnormal chromosomes, designated 11p+ and 14q-. To investigate the mechanism of t(11;14)(p13;q11) formation, we analyzed the translocation junctions of 11p+ and 14q- from two patients. The 11p+ junctions consisted of precise fusions of a pseudo recombination signal from chromosome 11 and the downstream recombination signal of the TCR D delta 2 gene segment from chromosome 14. In contrast, the 14q- junctions from both patients were diversified by random loss and addition of nucleotides at the translocation site. This asymmetric pattern of junctional diversification is typical of normal Ig/TCR gene rearrangement, and therefore implies that the t(11;14)(p13;q11) translocation arose due to aberrant activity of the Ig/TCR recombinase.
Adult↗
Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia.
The tal-1 gene is altered as a consequence of the t(1;14) (p32;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). tal-1 encodes a helix-loop-helix (HLH) domain, a DNA binding and dimerization motif found in a number of proteins involved in cell growth and differentiation. We now report that an additional 25% of T-ALL patients bear tal-1 gene rearrangements that are not detected by karyotype analysis. These rearrangements result from a precise 90 kb deletion (designated tald) that arises independently in different patients by site-specific DNA recombination. Since the deletion junctions resemble the coding joints of assembled immunoglobulin genes, tald rearrangements are likely to be mediated by aberrant activity of the immunoglobulin recombinase. Moreover, t(1;14)(p32;q11) translocations and tald rearrangements disrupt the coding potential of tal-1 in an equivalent manner, and thereby generate a common genetic lesion shared by a significant proportion of T-ALL patients.
Base Sequence↗
The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.
We have analyzed t(1;14)(p32;q11) chromosome translocations from two patients with T cell acute lymphocytic leukemia. The chromosome 1 breakpoints of these patients lie within a kilobasepair of each other, and thus define a genetic locus (designated tal) involved in T cell oncogenesis. Moreover, we have identified sequences within tal that potentially encode an amphipathic helix-loop-helix motif, a DNA-binding domain found in a variety of proteins that control cell growth and differentiation. The homology domain of tal is especially related to that of lyl-1, a gene on chromosome 19 that has also been implicated in T cell oncogenesis. Hence, tal and lyl-1 encode a distinct family of helix-loop-helix proteins involved in the malignant development of lymphocytes.
Amino Acid Sequence↗
The change in importance of hospital purchase decision criteria as a result of prospective payment.
Changes in the importance of various hospital purchase decision criteria as a result of prospective payment were explored. The purchasing agents in the survey reported that product price and an administrator's request were more important with prospective payment while the familiarity of the sales representative declined in importance.
Attitude of Health Personnel↗